TY - JOUR

T1 - Innovative Platform for the Advanced Online Monitoring of Three-Dimensional Cells and Tissue Cultures

AU - Kreß, Sebastian

AU - Schaller-Ammann, Roland

AU - Feiel, Jürgen

AU - Wegener, Joachim

AU - Priedl, Joachim

AU - Dietrich, Wolf

AU - Kasper, Cornelia

AU - Egger, Dominik

N1 - Funding Information: Funding: This research was funded by Österreichische Forschungsförderungsgesellschaft, grant number 859279.

PY - 2022/1/25

Y1 - 2022/1/25

N2 - The use of 3D cell cultures has gained increasing importance in medical and pharmaceutical research. However, the analysis of the culture medium is hardly representative for the culture conditions within a 3D model which hinders the standardization of 3D cultures and translation of results. Therefore, we developed a modular monitoring platform combining a perfusion bioreactor with an integrated minimally invasive sampling system and implemented sensors that enables the online monitoring of culture parameters and medium compounds within 3D cultures. As a proof-of-concept, primary cells as well as cell lines were cultured on a collagen or gelatin methacryloyl (GelMA) hydrogel matrix, while monitoring relevant culture parameters and analytes. Comparing the interstitial fluid of the 3D models versus the corresponding culture medium, we found considerable differences in the concentrations of several analytes. These results clearly demonstrate that analyses of the culture medium only are not relevant for the development of standardized 3D culture processes. The presented bioreactor with an integrated sampling and sensor platform opens new horizons for the development, optimization, and standardization of 3D cultures. Furthermore, this technology holds the potential to reduce animal studies and improve the transferability of pharmaceutical in vitro studies by gaining more relevant results, bridging the gap towards clinical translation.

AB - The use of 3D cell cultures has gained increasing importance in medical and pharmaceutical research. However, the analysis of the culture medium is hardly representative for the culture conditions within a 3D model which hinders the standardization of 3D cultures and translation of results. Therefore, we developed a modular monitoring platform combining a perfusion bioreactor with an integrated minimally invasive sampling system and implemented sensors that enables the online monitoring of culture parameters and medium compounds within 3D cultures. As a proof-of-concept, primary cells as well as cell lines were cultured on a collagen or gelatin methacryloyl (GelMA) hydrogel matrix, while monitoring relevant culture parameters and analytes. Comparing the interstitial fluid of the 3D models versus the corresponding culture medium, we found considerable differences in the concentrations of several analytes. These results clearly demonstrate that analyses of the culture medium only are not relevant for the development of standardized 3D culture processes. The presented bioreactor with an integrated sampling and sensor platform opens new horizons for the development, optimization, and standardization of 3D cultures. Furthermore, this technology holds the potential to reduce animal studies and improve the transferability of pharmaceutical in vitro studies by gaining more relevant results, bridging the gap towards clinical translation.

KW - 3D culture

KW - 3R

KW - Analytics

KW - Cells

KW - Microenvironment

KW - Monitoring platform

KW - Open flow microperfusion

KW - Perfusion bioreactor

KW - Sampling

KW - Sensors

UR - http://www.scopus.com/inward/record.url?scp=85123301631&partnerID=8YFLogxK

U2 - 10.3390/cells11030412

DO - 10.3390/cells11030412

M3 - Article

AN - SCOPUS:85123301631

VL - 11

JO - Cells

JF - Cells

SN - 2073-4409

IS - 3

M1 - 412

ER -